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The aim of this study is to elucidate if the anti-depressive effect of N,N-dimethyltryptamine (DMT) is based on a biological mechanisms including neuroplasticity and anti-inflammatory effect or due to the subjective psychedelic experience.
Major depressive disorder (MDD) affects nearly 20% of people, but current treatments-both pharmacological and psychotherapeutic-have limited efficacy, especially for mild to severe cases. Psychedelics like LSD, psilocybin, and DMT are being explored as alternative therapies, with studies showing promising antidepressant effects. However, it is unclear whether these benefits stem from their acute subjective (psychedelic) experience or from biological mechanisms like neuroplasticity and anti-inflammatory effects.
This study aims to determine if the antidepressant effects of DMT occur independently of its psychedelic experience. To test this, DMT will be administered under sedation (with propofol) to mask subjective effects, as well as without sedation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DMT without sedation | Experimental | DMT without sedation (propofol) |
|
| DMT with sedation | Experimental | DMT with sedation (propofol) |
|
| Placebo without sedation | Placebo Comparator | Placebo (double-blind) without sedation (propofol) |
|
| Placebo with sedation | Placebo Comparator | Placebo (double-blind) with sedation (propofol) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N,N-Dimethyltryptamine | Drug | administration of a 2mg/min DMT perfusion over 20 min |
|
| Measure | Description | Time Frame |
|---|---|---|
| long term changes in depressive symptoms (MADRS) | Changes in depressive symptoms will be assessed using Montgomery-Asberg-Depression Rating Scale (MADRS). The MADRS is a ten-item questionnaire widely used to measure severity of depressive symptoms during the last week. Total score (range 0-60); higher scores indicate greater depression severity. | baseline (before intervention) and on day 14 post-intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Short term changes in depressive symptoms (MADRS) | Changes in depressive symptoms will be assessed using Montgomery-Asberg-Depression Rating Scale (MADRS). The MADRS is a ten-item questionnaire widely used to measure severity of depressive symptoms during the last week. Total score (range 0-60); higher scores indicate greater depression severity. | Baseline (before intervention) and on day 1, 3 and 7 post-intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joyce Santos de Jesus | Contact | +41 61 556 65 02 | DMT4D@usb.ch |
| Name | Affiliation | Role |
|---|---|---|
| Matthias Liechti, Prof. Dr. med. | University Hospital, Basel, Switzerland | Study Director |
| Felix Müller, PD Dr. med. | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Recruiting | Basel | 4031 | Switzerland |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D004130 | N,N-Dimethyltryptamine |
| D015742 | Propofol |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D000588 | Amines |
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This study uses a randomized, double-blind (DMT vs placebo), placebo-controlled, 2x2 factorial parallel group design. Participants are randomly assigned to DMT or placebo (double-blinded) under either sedation with propofol or no sedation (sinlge-blinded).
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DMT and placebo will be administered in a double-blind fashion. However, investigators immediately involved in the treatment of the specific patient will be informed whether the assignment involves propofol or not. Participants will not be informed about the propofol assignment (single-blind).
| Placebo | Drug | administration of a placebo perfusion over 20 min |
|
| Propofol | Procedure | 30 min propofol sedation |
|
| no sedation | Procedure | no sedation |
|
| Changes in depressive symptoms (BDI) | Changes in depressive symptoms will be assessed using Beck Depression Inventory (BDI) questionnaire. Total score (range 0-63); higher scores indicate more severe depressive symptoms. | Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention |
| Changes in anxiety (STAI) | Changes in anxiety will be assessed using the self-reported State-Trait Anxiety Inventory (STAI) questionnaire. Separate total scores for State Anxiety (S-Anxiety) and Trait Anxiety (T-Anxiety) (each range 20-80); higher scores indicate greater anxiety. | Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention |
| Changes of clinical global impression (CGI-S) | The clinical global impression (CGI) is an instrument for the assessment of the patient's overall functioning both before and after starting the treatment. Severity of Illness (CGI-S): Rated on a 7-point scale (1 = normal, 7 = among the most extremely ill). | Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention |
| Changes of clinical global impression (CGI-I) | The clinical global impression (CGI) is an instrument for the assessment of the patient's overall functioning both before and after starting the treatment. Improvement (CGI-I): Rated on a 7-point scale (1 = very much improved, 7 = very much worse). | Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention |
| Changes in quality of life (WHOQOL-bref) | Changes in quality of life will be assessed by World Health Organization Quality of life scale (WHOQOL-bref). The WHOQOL-bref is one of the most commonly used self-rating instruments for the assessment of the quality of life and covers different domains of quality of life (physical, psychological, level of independence, social relationships, and environment, and spirituality). Domain scores (Physical, Psychological, Social, Environmental), scaled from 0 to 100; higher scores indicate better quality of life. | Baseline (before intervention) and on day 1, 3, 7 and 14 post-intervention |
| Persisting positive and negative effects (PEQ) | Psychedelics have been shown to produce persisting effects on well-being and appreciation of social relationships on the PEQ.This questionnaire will be used at the EOS visit to assess similar persisting effects of the DMT experience in addition to any effects on depressive symptomatology. Subscale scores (e.g., positive attitudes, mood changes, spirituality), typically rated 0-5 or 0-6; higher scores indicate stronger persisting effects. | On day 14 post-intervention |
| Acute subjective effects (5D-ASC) | The 5 Dimensions of Altered States of Consciousness (5D-ASC) Scale is a questionnaire containing visual analog scales for 94 items. The instrument contains five scales assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Each item of the scale is scored on a 0-100 mm VAS. Scores for 5 dimensions (e.g., Oceanic Boundlessness, Anxious Ego Dissolution), range typically 0-100%; higher scores indicate more intense altered states. | On day 0 post-intervention |
| Subjective Effects Rating (SES) | Participants will be asked by the investigator to repeatedly rate their subjective effects verbally on a Likert scale from 0 to 10 for: "any drug effect", "good drug effect", "bad drug effect", and "fear". Ratings will be performed before and repeatedly after substance administration and will take approximately 30 sec to complete. The time course and maximal ratings (Emax, 0-10) are defined for each rating and Emax values compared between treatments using analysis of variance (ANOVAs). Total and subscale scores (range and subscales vary by implementation); higher scores indicate more intense subjective effects. | On day 0 pre- and post-intervention |
| Psychedelic Experience Scale (PES) | In the PES, 100-items are rated on a six-point scale. The PES represents a revalidation of the original 100-item States of Consciousness Questionnaire (SOCQ) | On day 0 post-intervention |
| Emotional breakthrough inventory (EBI) | The Emotional breakthrough inventory (EBI) is a validated instrument with 6 items to assess the degree of emotional breakthrough as a distinct component of the acute psychedelic experience. Total score (range varies); higher scores indicate stronger emotional breakthrough experiences. | On day 0 post-intervention |
| Acute adverse effects | Acute adverse effects wil be assessed by the List of complaints (LC). LC is a self-reporting tool to assess physical and general discomfort. A revised version is used which consists of a 40-item list covering a wide variety of symptoms and complaints that are answered with a four-point intensity-scoring ranging from "not at all" to "strong". Total number or severity of reported somatic and psychological complaints will be evaluated. | On day 0 and 1 post-intervention |
| Safety events | Adverse events will be assessed over the whole study period. | From day 0 to day 14 post-intervention |
| Neuroplasticity | brain-derived neurotrophic factor (BDNF), a biomarker for neurogenesis will be quantified in blood samples collected before and 14 days after intervention | Baseline (before intervention) and on day 14 post-intervention |
| Inflammation | Interleukin-1 beta (IL-1β) an immunological factor linked to depression will be quantified in blood samples collected before and 14 days after intervention | Baseline (before intervention) and on day 14 post-intervention |
| DMT plasma concentration | Plasma levels of DMT will be measured once shortly before the end of the perfusion | On day 0 shortly before the end of the perfusion |
| Expectancy (CEQ) | Expectancy will be assessed before the first drug administration. Thus, patients will know at this timepoint whether they get the treatment with or without propofol. To measure expectancy, a modified 2-item version of the Credibility / Expectancy Questionnaire (CEQ) is used. Credibility score (range 3-27). | At Baseline before intervention |
| Expectancy | The Stanford Expectations of Treatment Scale (SETS) will evaluate positive and negative expectancies. Expectancy score (range 3-27 or expressed as a probability %). | At Baseline before intervention |
| Mood | The Adjective Mood Rating Scale (AMRS) is a self-rating scale assessing current mood states. The AMRS will be used to assess mood before the DMT experience. Positive mood and greater acute well-being is expected to positively enhance the acute DMT effects as similarly shown for other psychedelics. Scores for multiple mood dimensions (e.g., energy, mood, agitation); higher scores reflect greater expression of that dimension. | At day 0 directly before administration of the study drug |
| Personality (NEO-FFI) | Personality traits are known to affect subjective responses to psychoactive substances. The NEO Five Factor Inventory (NEO-FFI) will be used during screening to self-assess personality traits. Scores for five domains (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness); raw or standardized T-scores. | At Baseline before intervention |
| Personality (TAS) | Personality traits are known to affect subjective responses to psychoactive substances. The Tellegen Absorption Scale (TAS) will be used during screening to self-assess personality traits. Total score (range 0-34 or 0-136, depending on version); higher scores indicate greater trait absorption. | At Baseline before intervention |
| Sedation Level (RASS) | Level of sedation will be assessed during propofol session after each administration using the validated Richmond Agitation-Sedation Scale (RASS). The RASS is an observer-rated clinical scale used to assess level of agitation and sedation in the intensive care unit. The scale ranges from "+4" (combative) through "0" (alert and calm) to "-5" (unarousable). Intermediate scores include "+3" (very agitation), "+2" (agitated), "+1" (restless), "-1" (drowsy), "-2" (light sedation), "-3" (moderate sedation), and "-4" (deep sedation). | On day 0 during intervention |
| D009930 |
| Organic Chemicals |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |